Bifidobacteria and the infant gut: an example of co-evolution and natural selection

Throughout the human life, the gut microbiota interacts with us in a number of different ways, thereby influencing our health status. The acquisition of such an interactive gut microbiota commences at birth. Medical and environmental factors including diet, antibiotic exposure and mode of delivery are major factors that shape the composition of the microbial communities in the infant gut. Among the most abundant members of the infant microbiota are species belonging to the Bifidobacterium genus, which are believed to confer beneficial effects upon their host. Bifidobacteria may be acquired directly from the mother by vertical transmission and their persistence in the infant gut is associated with their saccharolytic activity toward glycans that are abundant in the infant gut. Here, we discuss the establishment of the infant gut microbiota and the contribution of bifidobacteria to this early life microbial consortium.     

Selected aspects of the human gut microbiota

The gut microbiota represents a highly complex assembly of microbes, which interact with each other and with their host. These interactions have various implications in terms of health and disease, and this multi-author review issue will address a number of selected aspects pertaining to gut microbiota research.     

A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism

Submicroscopic genomic copy number changes have been identified only recently as an important cause of mental retardation. We describe the detection of three interstitial, overlapping 17q21.31 microdeletions in a cohort of 1,200 mentally retarded individuals associated with a clearly recognizable clinical phenotype of mental retardation, hypotonia and a characteristic face. The deletions encompass the MAPT and CRHR1 genes and are associated with a common inversion polymorphism.     

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.     

Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins

A large range of debilitating medical conditions is linked to protein misfolding, which may compete with productive folding particularly in proteins containing multiple domains. Seventy-five per cent of the eukaryotic proteome consists of multidomain proteins, yet it is not understood how interdomain misfolding is avoided. It has been proposed that maintaining low sequence identity between covalently linked domains is a mechanism to avoid misfolding. Here we use single-molecule F?rster resonance energy transfer to detect and quantify rare misfolding events in tandem immunoglobulin domains from the I band of titin under native conditions. About 5.5 per cent of molecules with identical domains misfold during refolding in vitro and form an unexpectedly stable state with an unfolding half-time of several days. Tandem arrays of immunoglobulin-like domains in humans show significantly lower sequence identity between neighbouring domains than between non-adjacent domains. In particular, the sequence identity of neighbouring domains has been found to be preferentially below 40 per cent. We observe no misfolding for a tandem of naturally neighbouring domains with low sequence identity (24 per cent), whereas misfolding occurs between domains that are 42 per cent identical. Coarse-grained molecular simulations predict the formation of domain-swapped structures that are in excellent agreement with the observed transfer efficiency of the misfolded species. We infer that the interactions underlying misfolding are very specific and result in a sequence-specific domain-swapping mechanism. Diversifying the sequence between neighbouring domains seems to be a successful evolutionary strategy to avoid misfolding in multidomain proteins.     

Fossil jawless fish from China foreshadows early jawed vertebrate anatomy

Most living vertebrates are jawed vertebrates (gnathostomes), and the living jawless vertebrates (cyclostomes), hagfishes and lampreys, provide scarce information about the profound reorganization of the vertebrate skull during the evolutionary origin of jaws. The extinct bony jawless vertebrates, or 'ostracoderms', are regarded as precursors of jawed vertebrates and provide insight into this formative episode in vertebrate evolution. Here, using synchrotron radiation X-ray tomography, we describe the cranial anatomy of galeaspids, a 435-370-million-year-old 'ostracoderm' group from China and Vietnam. The paired nasal sacs of galeaspids are located anterolaterally in the braincase, and the hypophyseal duct opens anteriorly towards the oral cavity. These three structures (the paired nasal sacs and the hypophyseal duct) were thus already independent of each other, like in gnathostomes and unlike in cyclostomes and osteostracans (another 'ostracoderm' group), and therefore have the condition that current developmental models regard as prerequisites for the development of jaws. This indicates that the reorganization of vertebrate cranial anatomy was not driven deterministically by the evolutionary origin of jaws but occurred stepwise, ultimately allowing the rostral growth of ectomesenchyme that now characterizes gnathostome head development.